Beutler Ernest, Duparc Stephan
The Scripps Research Institute, La Jolla, California 92037, USA.
Am J Trop Med Hyg. 2007 Oct;77(4):779-89.
Glucose-6-phosphate dehydrogenase (G6PD) deficiency is relatively common in populations exposed to malaria. This deficiency appears to provide some protection from this infection, but it can also cause hemolysis after administration of some antimalarial drugs, especially primaquine. The risk of drug-induced G6PD deficiency-related hemolysis depends on a number of factors including the G6PD variant, the drug and drug dosage schedule, patient status, and disease factors. Although a great deal is known about the molecular biology of G6PD, determining the potential for drug-induced hemolysis in the clinical setting is still challenging. This report discusses the potential strategies for assessing drug-induced G6PD deficiency-related hemolytic risk preclinically and in early clinical trials. Additionally, the issues important for conducting larger clinical trials in populations in which G6PD deficiency is prevalent are examined, with a particular focus on antimalarial drug development.
葡萄糖-6-磷酸脱氢酶（G6PD）缺乏症在疟疾流行地区相对常见。这种缺乏症似乎能为预防这种感染提供一定保护，但在使用某些抗疟药物（尤其是伯氨喹）后也可能导致溶血。药物诱导的G6PD缺乏症相关溶血的风险取决于多种因素，包括G6PD变体、药物及药物给药方案、患者状况和疾病因素。尽管人们对G6PD的分子生物学已经有了很多了解，但在临床环境中确定药物诱导溶血的可能性仍然具有挑战性。本报告讨论了在临床前和早期临床试验中评估药物诱导的G6PD缺乏症相关溶血风险的潜在策略。此外，还研究了在G6PD缺乏症普遍存在的人群中开展更大规模临床试验的重要问题，特别关注抗疟药物的研发。
